This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given together with GDC-0449 with or without gemcitabine hydrochloride in treating patients with metastatic pancreatic cancer or solid tumors that cannot be removed by surgery. Drugs used in chemotherapy, such as GDC-0449 and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving GDC-0449 together with erlotinib hydrochloride with or without gemcitabine hydrochloride may kill more tumor cells.

The number and severity of all adverse events (overall, and by dose-level) will be tabulated and summarized.

Response as assessed by modified RECIST criteria [ Time Frame: Up to 3 months after completion of study treatment ] [ Designated as safety issue: No ]

Summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease.

Time to progression [ Time Frame: Up to 3 months after completion of study treatment ] [ Designated as safety issue: No ]

Time to treatment failure [ Time Frame: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months after completion of study treatment ] [ Designated as safety issue: No ]

Time until hematologic nadirs (WBC, ANC, platelets) [ Time Frame: Up to 3 months after completion of study treatment ] [ Designated as safety issue: No ]

Toxicity, defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment, graded using the NCI CTCAE version 3.0 [ Time Frame: Up to 3 months after completion of study treatment ] [ Designated as safety issue: Yes ]

Patients receive Hedgehog antagonist GDC-0449 PO QD and erlotinib hydrochloride PO QD on days 1-28. Some patients also receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Diagnostic Laboratory Biomarker Analysis

Correlative studies

Drug: Erlotinib Hydrochloride

Given PO

Other Names:

Cp-358,774

ERLOTINIB HYDROCHLORIDE

OSI-774

Tarceva

Drug: Gemcitabine Hydrochloride

Given IV

Other Names:

dFdCyd

Difluorodeoxycytidine Hydrochloride

GEMCITABINE HYDROCHLORIDE

Gemzar

LY-188011

Drug: Vismodegib

Given PO

Other Names:

Erivedge

GDC-0449

Hedgehog Antagonist GDC-0449

VISMODEGIB

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of erlotinib hydrochloride and Hedgehog antagonist GDC-0449 with or without gemcitabine hydrochloride in patients with unresectable solid tumors.

SECONDARY OBJECTIVES:

I. To describe the adverse events profile associated with these treatment regimens.

II. To describe the responses in patients treated with these regimens. III. To assess the effect of erlotinib hydrochloride and Hedgehog antagonist GDC-0449 on selected biomarkers in circulating tumor cells and tumor biopsy samples from patients with metastatic pancreatic cancer.

Patients receive Hedgehog antagonist GDC-0449 orally (PO) once daily (QD) and erlotinib hydrochloride PO QD on days 1-28. Some patients also receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients treated at the maximum tolerated dose undergo fludeoxyglucose F 18 positron emission tomography at baseline and on day 28. These patients also undergo tumor tissue and blood sample collection at baseline and periodically during study for correlative laboratory studies. Samples are analyzed for tyrosine phosphorylated or total MAP-K, EGFR, AKT, and other potential biomarkers of activity/response and for levels of genes transcriptionally activated (e.g., BCL-2, GLI, BFL-1/A1, 4-1BB, PTC1) by immunofluorescence, IHC, and quantitative-PCR.

After completion of study therapy, patients are followed at 3 months.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Histologic proof of a solid tumor that is now unresectable, not amenable to any other standard therapies, or patient refuses standard therapy

Failure to fully recover from acute, reversible effects of prior therapy regardless of interval since last treatment

New York Heart Association classification III or IV

Seizure disorder

Central nervous system (CNS) metastases if not stable for at least 2-3 months based on imaging, clinical assessment, and use of steroids, or seizure disorder

Pregnant women

Nursing women

Men or women of childbearing potential who are unwilling to employ adequate contraception until 12 months after last study drug dose

Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)

Current therapy with a CYP3A4 inhibitor or inducer

Immunocompromised patients (other than that related to the use of corticosteroids) including patients receiving highly active antiretroviral therapy (HAART) treatment

Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

Active other malignancy, excepting non-melanotic skin cancer or carcinoma-in-situ of the cervix; if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer

More than 2 prior chemotherapy regimens for the current metastatic malignancy; full dose chemotherapy used in conjunction with concurrent radiation therapy will be included as prior therapy; Note: prior hormonal therapy (e.g. leuprolide, aromatase inhibitors, tamoxifen) will be allowed and not included as a prior chemotherapy

Previous therapy with a hedgehog inhibitor

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00878163